High density lipoprotein (HDL) concentrations are significantly lower in the plasma of human and non-human primates consuming diets enriched in polyunsaturated fatty acids(PUFA) compared to saturated or mono- unsaturated fat. The decrease in concentration appears to occur in apoA-I only HDL particles (LpA-I) with little change in LpA-I/A-II (particles containing both apoA-I and A-II). The goal of this project is to elucidate the basic mechanisms by which dietary fat saturation affects HDL production and catabolism. Our preliminary studies have shown that there is unidirectional conversion of small LpA-I (2 A-I per HDL) to medium (3 A-I per HDL) and large LpA-I (4 A-I per HDL) in vivo in African green monkeys, and that animals with low HDL have one fourth the conversion rate of small to large LpA-I compared to those with high HDL concentrations. We hypothesize that diet rich in PUFA compared to those containing saturated and mono-unsaturated fat lead to decreased production of small LpA-I and/or to decreased conversion of the small LpA-I to medium and large LpA- I. Alternatively, PUFA-rich diets may result in a faster catabolism of LpA-I from plasma. The decreased production of small LpA-I in animals led PUFA diets may result from decreased stability of apoA-I on HDL particles that contain PUFA, leading to poor assembly of apoA-I with lipid and hypercatabolism of lipid-free or lipid-poor apoA-I. In specific aim 1, in vivo catabolism studies with plasma LPA-I will be performed in African green monkeys to test the hypothesis that PUFA diets compared to saturated or mono-unsaturated fat lead to decreased LpA-I by the decreased production of small LpA-I and/or the decreased conversion of small LpA-I derived from African green monkeys will be performed to test the hypothesis that PUFA diets result in decreased conversion of nascent discoidal LpA-I secreted by the liver to spherical LpA-I. In specific aim 3, studies will be performed to test they hypothesis that PUFA diets result in a reduction of nascent LpA-I particles due to decreased intracellular and/or extracellular assembly of apoA-I with phospholipid. The basic information from this study will lead to a better understanding of HDL metabolism and could b tested to make more rational decisions concerning dietary treatment of individuals at risk for CHD.